Cystadenoma and Cystadenocarcinoma of the Pancreas Eddy S. Muzac, MD Nashville, Tennessee
Cystadenomas and cystadenocarcinomas of the pancreas are rare, with few cases encountered by any one surgeon or institution. Cystadenomas account for less than ten percent of all cystic lesions of the pancreas with less than 300 examples reported in the literature. Cystadenocarcinomas represent one percent of all pancreatic cancers with very few cases reported. This report is a presentation of a 48-year-old black female who was treated at Meharry Medical College for cystadenocarcinoma of the pancreas, and is followed by a review of the world literature. Cystic lesions of the pancreas are generally rare. Proliferative cysts of the pancreas-cystadenoma and cystadenocarcinoma-are exceptionally rare. Very few cases have been reported in the literature. Because of the rarity of these lesions, the experience of any surgeon or institution is necessarily limited; thus these lesions always constitute an interesting and challenging problem. We report a case of cystadenocarcinoma of the pancreas, which was treated at the G. W. Hubbard Hospital of Meharry Medical College. This presentation is followed by a review of the world literature.
Case Report A 48-year-old black female was referred to the surgical service on February 23, 1977, because of an abdominal mass which she had first noted when lying prone about two weeks after Thanksgiving 1976. A few weeks later, she was able to feel the mass with her hand. The mass grew gradually to become a huge tumefaction filling the entire left aspect of the abdomen from the pelvis to the costal margin. She gave a history of occasional left flank pain which radiated to the anterior ab-
From the Department of Surgery, Meharry Medical College, Nashville, Tennessee. Requests for reprints should be addressed to Dr. Eddy S. Muzac, Department of Surgery, Meharry Medical College, 1005 18th Avenue North, Nashville, TN 37208.
domen. It was mild, lasted about one to two days, and dated back to September 1976. There was no history of nausea, vomiting, diarrhea, constipation, or bleeding from any orifice. There were no indications of trauma, pancreatitis, or drug addiction. There was a history of amenorrhea one month prior to admission and of a 20 lb weight loss in four months. She was para 3, gravida 3, and had had no abortions. Her menarche was at age 15 years; she experienced regular menses. There was no previous hospitalization or surgery, or history of diabetes mellitus, heart disease, or other systemic disease. Pertinent physical findings revealed moderate tachycardia with regular rhythm and an ejection murmur prominent at the apex with no gallop. The abdomen revealed a 25 x 20 cm tumefaction which extended from the pelvis to the costal margin and across the midline and filled the left anterolateral aspect of the abdomen. On palpation it was firm, irregular, nonmobile, and nontender. The superior surface was suggestive of a cystic lesion. There were no bruits or pulsation. On pelvic examination, movement of the cervix did not mobilize the tumor. The cervix was large and deviated to the left, but the uterus was not appreciably enlarged. Diagnostic studies revealed that blood morphology and chemistry values were normal except for a slight normocytic, normochromic anemia, SGOT of 81 m,u/ml, and a CEA of 1,125 ng/ml. A chest x-ray was normal except
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for elevation of the left hemidiaphragm. A flat plate x-ray examination of the abdomen revealed a large soft tissue mass in the left flank with a questionable calcification in the center. Intravenous pyelogram (IVP) showed deviation of the right ureter. Slight left side hydronephrosis was suggestive of compression of the left ureter by the abdominal mass. Barium enema showed marked depression of the splenic flexure and transverse colon. The upper gastrointestinal (UGI) series showed displacement and rotation of the stomach to the right with indention. Abdominal ultrasound showed a mass located in the upper compartments of the abdomen, which was not of ovarian or uterine origin. Spleen scan showed no involvement of that organ by the mass. The patient underwent exploratory surgery on March 3, 1977. A mass filling the entire left side of the abdomen was identified. It extended between the left side of the diaphragm superiorly, the pelvis inferiorly, and the right midclavicular line medially. The mass was cystic, partially covered by the gastrocolic omentum, and attached to the left hemidiaphragm, to the spleen which was in fact incorporated, and to the pancreatic tail (Figure 1). The stomach was displaced medially and the splenic flexure and transverse colon, inferiorly. The mass was anterior to the kidney. Both ovaries, the uterus (which was small), the liver, and the gallbladder were normal. The cyst was opened and five liters of light brown material were drained. Specimens were sent for culture and cytology. The interior lining of the cyst presented numerous papillary excrescences which were biopsied and sent for frozen section along with a mesenteric lymph node. The mass was resected, together with the spleen and the liver, and clips were placed in its bed before closing the abdomen in layers. The immediate postoperative course was uneventful. The pathologic diag495
Figure 1. Gross presentation of cystadenocarcinoma of the pancreas. Unilocular cyst with papillary excrescences in the cyst cavity
of the pancreas. Such a classification would present the pancreatic cysts in two principal groups: simple cysts and proliferative cysts. The latter would then essentially include cystadenoma and cystadenocarcinoma along with the very rare teratoma and vascular tumor. A classification based upon etiologic considerations, used by Vezzosi," includes five groups: (1) congenital cysts, (2) pseudocysts (traumatic or inflammatory), (3) retention cysts, (4) parasitic cysts, and (5) proliferative cysts (cystadenoma, cystadenocarcinoma). This classification is not different from that of Mahormer and Mattson as modified by Catell and Warren.'2 Personally, this author prefers the classification presented by Mallet-Guy and Mercadier in 1958 as cited by Ribet et al'3 (Table 1).
Incidence nosis was papillary cystadenocarcinoma of the pancreas (Figure 2). Following surgery, the patient received a course of chemotherapy (5FU). She was discharged in satisfactory condition. The CEA level was 520 in March and 136 in April. She was given 4,500 rads to the area outlined by clips. Subsequently, she received several courses of 5-FU until September 1977 when it was changed to mitomycin C. She was hospitalized in December 1977 for melena and upper gastrointestinal bleeding. Esophagogastroduodenoscopy showed bleeding from the stomach and duodenum. She died on January 10, 1978, of massive hemorrhage. An autopsy was not performed.
Discussion According to Adloff,' the first description of a pancreatic cystadenoma was given by Cruveilhier in 1863. In 1891, Hartmann,2 in France, described a cystadenoma of the pancreas with metastases to the liver. Sotti,3 in 1906 in Italy, presented a papillary cystadenoma with a spread to the peritoneum, the lungs, and regional 496
nodes. Lichtenstein4 in 1934 reported the first authentic case of cystadenocarcinoma of the pancreas recorded in America. Kennard5 presented the first review of the literature of cystadenocarcinoma of the pancreas in 1941, and found 25 documented cases. In 1951, Mozan' published an excellent review of the literature of cystadenoma of the pancreas and discussed 49 firmly documented cases, including one of his own. In 1963, Cullen et a17 reported the Mayo Clinic's experience with neoplastic cysts of the pancreas between 1908 and 1963. In 1965, Becker et all presented the experience of the Charity Hospital and of three other New Orleans hospitals for a 27-year period from 1938 through 1964. He found 164 recorded cases of cystadenoma and 65 cases of cystadenocarcinoma in the literature, since the first case reported by Frantz Lahey in 1927 (cited by Warren and Hardy).9 In 1971, in a presentation of the subject, Lewis and Dormandy'° could only record 251 cases of cystadenoma. The total cases reported in
the literature consist of approximately 300 cystadenomas and 130 cystadenocarcinomas. As part of a group of cystic formations, it becomes very useful to study the classification of cystic lesions
Haukolh and Melamed'4 emphasized that the true incidence of pancreatic cystadenoma and cystadenocarcinoma could not be known since many cases were undoubtedly buried in reports on pancreatic surgery, listed under erroneous diagnoses, or included in reports of unrelated nonneoplastic cysts. However, it is generally admitted that these lesions are rare. Cystadenomas account for approximately ten percent of all cystic lesions of the pancreas and are twice as frequent as cystadenocarcinomas. The latter are responsible for about one percent of all pancreas cancers. Bravo'5 could find records of only six cystadenocarcinomas in 202 cases of primary carcinoma of the pancreas at the Mayo Clinic. Cornes and Azzopardi'6 reported only two papillary cystadenocarcinomas in 8,500 necropsies at the Postgraduate Medical School of London in a 23-year-period. Rowe'7 reported one case of cystadenocarcinoma of the pancreas in more than 300,000 admissions to the Montreal General Hospital. Becker et a18 recorded seven cystadenomas and two cystadenocarcinomas in 2,184,427 admissions to Charity Hospital, New Orleans, during a 27-year-period. Warren and Hardy9 at the Lahey Clinic could find only 17 cystadenocarcinomas in 993 operations involving the pancreas during a 40-year-
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period. Warren and Badosa,18 at the same institution, reported only 12 cystadenomas and 15 cystadenocarcinomas in 256 patients with pancreatic cysts between 1927 and 1971. Darmaillac,19 Priesel,20 and Mercadier21 have also shown the rarity of these lesions. Our case of cystadenocarcinoma is the only one ever recorded at the G.W. Hubbard Hospital at Meharry Medical College in Nashville. All of the authors have emphasized the frank predominance of the proliferative cysts cystadenoma-cystadenocarcinoma-in women. Almost universally, these tumors occur in patients younger than those with solid carcinoma of the pancreas, which usually occurs in the fifth or sixth decade.
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Histogenesis The origin of the cystadenomas is uncertain. Although they constitute definite pathologic entities, very little is known of their pathogenesis. Trauma and inflammation apparently play no role in their formation. Glenner and Mallory,22 in a classic paper, state they have demonstrated that cystadenomas originate from the pancreatic ductal epithelium and describe the lesion as being true ductal cell adenomas of the cystic type. They classify nonfunctional pancreatic adenomas as duct adenomas, acinar adenomas, mixed adenomas, and fibroadenomas and include cystadenomas with solid duct cell adenomas. They state that the nonfunctional pancreatic adenomas originate deep in the parenchyma of the pancreas whereas cystic duct cell adenomas (cystadenomas) originate more peripherally.
Pathology The most common locations of the cyst, according to the majority of authors, are the tail and the body of the pancreas. As a matter of fact, of 81 cases of Becker,23 39 involved the tail of the glands, 14 the body, and 15 the head. There were ten cases of diffuse involvement of the pancreas. Cullen et a17 give the following distribution of 16 cases: body, four; head, three; tail, three; body and tail, two; and head and body, one. Theoretically, according to Becker et a18 these lesions may arise from heterotopic tissue; however, such
Figure 2. Microscopic appearance of papillary cystadenocarcinoma of the pancreas
cases were not described in the series. According to Kennard,5 the most common position into which the cyst grows is between the stomach and the transverse colon. Of 11 cases of Cullen et al,7 the presentation was behind the stomach in four; below the stomach through the gastrocolic omentum in two; in one case, above the stomach, through the gastrohepatic omentum below the transverse colon; and in one case, between the leaves of the transverse mesocolon, behind the transverse colon, and extending into the pelvis underneath the omentum to fill the entire left side of the abdomen. Mozan6 has described many types of cysts, ranging in size from very small to huge. The cases of Cullen7 vary from 8 to 24 cm in diameter. The character of the cyst content varies considerably. Often it is mucoid or serous and rarely clear. It has been described by different authors as thick colloid jelly,7 cloudy,9 straw colored, greenish, grayish, brown, or bloody,5 and chocolate or light brown in color. The volume of fluid varies in proportion to the size of the cyst, from 100 ml to gallons of fluid ("considerable fluid"'). In our case, the cyst cavity contained four to six liters of light brown material. One or more pancreatic enzymes may be found in the fluid, as reported by Kennard.5
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The gross appearance of pancreatic cystadenomas is fairly characteristic. Its surface is irregular, presenting a polycystic aspect. Very often, the tumor is surrounded by widely dilated veins due to local pressure, presumably from compression of the splenic vein. These vessels may constitute a serious obstacle to the surgeon at the time of operation. This vascularity was a feature of our case. Depending upon the size and location of the tumor, there may or may not be considerable distortion and/or displacement of the surrounding viscera. The cut surface is almost classical and demonstrates the different morphological varieties of cyst. Indeed one can find the uniloculated (serous of Mercadier), the pauciloculated (few cavities), and the multiloculated (numerous cavities) cysts or mucoid cysts. The uniloculated cyst is typical for Mercadier.21 The multiloculated is the classical form described in most pathology treatises. This is the centroacinar cystadenoma of Becker et al.8 The tumor is occasionally less markedly cystic, grossly presenting a softer, more cellular yellowish-gray cut surface. This is the papillary cystadenoma in which the cyst is filled with irregular papillary masses or excrescences. The papillary excrescences have been 497
Table 1. Classification of Pancreatic Cysts13
I. Pseudocysts 1. Traumatic 2. Apoplectic 11. Retention Cysts 1. Obstruction by stone 2. Obstruction by neoplasm 3. Obstruction by scar Ill. True Cyst 1. Embryonic cysts A. Ectodermal or dermoid B. Endodermal or enteroid C. Ecto and endodermal cystic teratoma 2. Neoplastic cysts (from acinar or ductal epithelium) A. Cystadenoma B. Cystadenocarcinoma 3. Parasitic cysts or hydatid cysts 4. Mesenchymatous cysts A. Hemangioma B. Lymphangioma C. Hemangioendothelioma
viewed by some authors as a sign of malignancy or potential malignancy. The overall appearance of cystadenoma and cystadenocarcinoma is identical. Only microscopic analysis may make the difference. However, one may suspect malignancy if the following signs are present: papillary excrescences in cyst cavity, invasion of surrounding organs, local lymph node involvement, and distant metastases. According to Warren and Hardy,9 common sites of metastases, when they occur, include the liver, peritoneum, lesser omentum, transverse mesocolon, spleen, and left kidney.
Microscopic Study The fibrous capsule of the cyst is generated by compression and progressive atrophy of the pancreatic lobules in contact with the tumor. It may still contain a few ducts and islands of Langerhans like any sclerotic process of the pancreas. The radiating trabeculae between the cyst have the same collagen consistency as the surrounding capsule to which they are connected. The oldest ones have become hyalosclerotic, poor in blood ves498
sels, and epithelial. Some others are more congestive and thick with more cellularity and epithelial destruction due to a mutilating inflammatory reaction. They may show signs of stromal calcification of varying importance probably due to the organization of small hemorrhages and inflammatory reactions. The lining of the cyst is variable from one case to another and may vary from one small unit to another one. In the most typical case, the lining cells are low cuboidal. True papillary formation does not appear here. These epithelial cells have been linked to the flat cells of the terminal ductules of the pancreas or to centroacinar cells. In some tumors the epithelium is so flattened as to resemble vascular epithelium. This, together with the scattering of lymphocytes in the stroma and some degree of hemorrhagic effusion in the cystic cavity, may mislead to the false diagnosis of cystic lymphangioma, angioendothelial sarcoma, or vascular tumor. However, generally repeated sections may reveal definite cuboidal epithelium and the true nature of the tumor. Finally, in certain cysts presenting intracystic papillary excrescences, the lining cells are columnar, resembling large pancreatic duct epithelium. The lining may also resemble intestinal epithelium or simulate the epithelium of
the pseudomucinous cystadenoma of the ovary. This type is papillary cystadenoma or proliferative cystadenoma. Certain authors feel that this is a premalignant form and believe that cystadenomas lined by tall columnar epithelium or intestinal-like epithelium are the ones which undergo malignant change and generate the cystadenocarcinomas. In cystadenocarcinomas, papillary growths of the lining epithelium are frequently seen but, while indicative of proliferative activity, are not by themselves sufficient for a diagnosis of malignancy in a cystadenoma of dubious appearance. 16 The criteria of malignancy have been well described by Cullen7 and Comes and Azzopardi. '6 These authors state that in the absence of metastases, perineural invasion, extracapsular extension, areas of frank anaplasia, or other unequivocal evidence of malignancy, evidence of malignant changes must be sought in the presence of focal areas showing pseudostratification or true stratification, nuclear hyperchromasia and irregularity, increase in nuclear size, mitotic activity, cellular differentiation, and presence of anaplastic areas with bizarre tumor cells and neoplastic giant cells.
Clinical Features The clinical features of pancreatic cystadenoma and cystadenocarcinoma are essentially those of a pancreatic cyst in general and are the result of pressure on contiguous structures by the slowly enlarging pancreatic tumor (Table 2). The evolution before diagnosis is generally progressive and insidious. Often the tumor will manifest itself after a long period of evolution. Becker et a18 state that over one third of patients had symptoms for more than 24 months before the diagnosis was established. The average duration of symptoms is, in general, approximately 18 months. The presence of an abdominal mass constitutes the most important clinical manifestation of the disease. It is reported in 80 to 90 percent of all cases. Often it is noticed by the patient himself; one study reported a 50 percent incidence of self discovery.8 The mass is found in the left upper quadrant or
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epigastrium in most instances. In the case of a tumor of the head of the pancreas, it may be felt in the right upper quadrant. Classically, the mass is irregular, firm, nontender, grossly round, and eventually nodular. This tumor is also mobile in more than 50 percent of cases, a feature which is so important that it becomes possible to mobilize the mass vertically and transversally. In certain instances, the mass may be palpated in the left lumbar area and mistaken for a renal mass, which may lead to a left lobotomy. Pain, the chief complaint in 50 percent of cases reported by Becker et al,8 is generally variable in location in the epigastrium or in the left upper quadrant. It may radiate to the back. Dyspepsia is recorded in 75 percent of cases and is generally manifested by flatulence (postcibal), nausea, and occasional vomiting. Diarrhea is reported in 15 percent of the cases and may lead one to think of a pancreatic involvement. The percentages given for weight loss by authorities differ widely; it was found in 25 percent of cases reported by Leborgne et al,24 and in 3 of 20 cases by Piper et al.25 In our patient, the weight loss was 25 lb in four months. Jaundice was present in 3 of 28 cases reported by Becker et al.8 It is generally explained on the basis of compression of the biliary system by a mass located in the head of the pancreas. Associated disorders, which include a case each of duodenal ulcer, pancreatitis, and jejunal diverticular, have been reported by Cullen et a17 in a review of 17 cases of cystadenocarcinoma. Some articles have additionally stressed the association of symptoms such as sterility, obesity, thyroid dysfunction, and diabetes mellitus with pancreatic cystadenomas. The complications of these tumors are related to their location and size and to the involvement of the surrounding organs from compression or infiltration by the neoplastic process. Compression of surrounding organs, ie, duodenal obstruction resulting from a
cystadenoma or cystadenocarcinoma located in the head of the pancreas, may occur. Common duct obstruction may occur through compression of its retropancreatic portion. This is seen more often in cystadenocarcinoma of the head of the pancreas. Hemorrhage may be one of the most severe complications of the lesions in the course of
their evolution. Different mechanisms may produce hemorrhage, such as segmental portal hypertension from compression or involvement of the splenic vein. Portal hypertension (segmental) is seen more frequently in tumors of the body of the pancreas.24 Infiltration of the gastric and the duodenal mucosa by cystadenocarcinoma with subsequent hemorrhage is frequently found.25 Cystadenoma in ectopic pancreatic tissue in the duodenum is listed by Leborgne et a124 as a possible cause of intestinal bleeding. Finally, intracystic hemorrhage remains a potential cause of bleeding in both cystadenoma and cystadenocarcinoma.24 Complications in the cysts themselves include intraperitoneal rupture and infection with abscess formation.
Diagnostic Procedures The laboratory is generally silent. In particular, the serum and urinary amylase are absolutely negative. However, instances of diabetic or paradiabetic states may be found. Besides, the hematology may be consistent with a certain degree of hypersplenism, particularly in the case of segmental portal hypertension with splenomegaly. The various radiographic studies may show the tumor in certain instances as a round homogenous mass modifying the gaseous patterns of the digestive tract. Exceptional cases may show striking calcification of the tumor. In a case reported by Haukolh and Melamed, 14 calcific deposits located in the head of the pancreas were arranged in a radiating "sunburst" pattern about a central, completely calcified nidus. Sometimes the calcifications appeared as small irregular particles scattered haphazardly throughout the tumor. Leborgne et a124 stated that calcifications are best diagnosed on lateral views and are present in only ten percent of cases. The UGI series may show displacement upward and forward of the stomach. Sometimes, in the case of a tumor of the head of the pancreas, the UGI series may show displacement of the antrum, duodenal stenosis, and/or widening of the C loop of the duodenum. Whipple (cited by Catell and Warren12) suggested giving barium simulta-
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Table 2. Signs and Symptoms % of Cases Abdominal mass Dyspepsia, nausea, vomiting Pain Weight loss Diarrhea Jaundice Diabetes
85 75 50 25 15 12 9
neously by mouth and rectum. X-ray will show the cyst bulging between the stomach and the transverse colon. The barium enema generally shows inferior displacement of the transverse colon and the splenic flexure. The cholangiography will demonstrate a compression of the common duct and the biliary system. The intravenous pyelogram shows signs of compression of the left ureter, which is sometimes accompanied by hydronephrosis (in the tail and body of the pancreas). Angiographic studies reveal important information concerning the nature and location of these tumors. Celiac and mesenteric selective arteriography have been described by Pinchuck,26 Swanson,27 Pressman,28 Lardennois et al,29 Ribet et al,13 and Debelut.30 Translumbar aortography has been used by Bieber and Albo.3' Lardennois29 has described a rupture of the arterial circle of the greater curvature of the stomach. The right gastroepiploic artery is pushed upward and to the right with the colon, resembling the letter S, the middle portion of the S being constituted by the hepatic artery and the splenic artery. This configuration is consistent with a retroperitoneal location of the tumor. The venous phase will show an extensive capillary blush in the tumor and occasional displacement of the portal vein. Certain signs, like hypervascularization of the tumor and the presence of hemorrhagic plaques inside the cyst, will indicate a malignant lesion. But these signs have been described in both cystadenoma and cystadenocarcinoma. In the case of a tumor of the distal pancreas, splenoportography is the best angio499
graphic exploration. Celiac and mesenteric selective arteriography may reveal the presence of a retro or intrapancreatic right hepatic artery which is found in 20 percent of cases.24 Its localization may be important if a duodenopancreatectomy is considered. Endoscopic retrograde cannulation of the pancreatic duct may greatly aid in the diagnosis of these tumors in the future. Splenic and pancreatic scan may show noninvolvement of the spleen and the relationship of the tumor with the pancreas. Ultrasonic characteristics of cystadenoma of the pancreas have also been explored: a sonolucent lesion with strong through transmission, silent irregularity of the wall, and an internal septum should suggest cystadenoma.2
vital structure like the portal vein or the splenomesenteric junction in the case of a very old patient or a patient with poor general condition. Warren and Hardy9 favor cystogastrostomy or cystojejunostomy. Mercadier21 states that a cystoduodenostomy is more physiologically functional. Survivals of several years have been reported after internal drainage for cystadenocarcinoma, which attests to the slow growing character of this tumor. Biopsy, frozen section, puncture, or opening of the cyst are not recommended because of the risk of spillage and seeding.
Radiotherapy As a palliative treatment, radiotherapy may be helpful in the case of extensive lesions or as an adjuvant therapy in addition to operation.9
Chemotherapy Treatment Treatment varies with the location of the lesion and the age and general condition of the patient. Surgical treatment is rather classical and includes several possibilities.
Definitive Surgical Treatment Enucleation of a cystadenoma may be possible if there is a definite capsule which will allow complete and easy removal en bloc. Excision with a margin of pancreatic tissue is advocated for both cystadenoma and cystadenocarcinoma. This procedure is very easy in the case of a pedunculated cyst with a small base. Distal pancreatectomy with splenectomy is advocated for tumors of the tail and body of the pancreas. Duodenopancreatectomy is the preferred treatment for lesions of the head of the pancreas. This is the price to pay to cover in the case of the benign variant (cystadenoma) because of serious potential degeneration. Total duodenopancreatectomy may be considered for diffuse lesions.
Palliative Surgical Treatment Marsupialization is not employed when one is operating for cure even in the case of cystadenoma. Risk of malignant degeneration is the reason for contraindication. Internal drainage considered as a palliative procedure would endanger a 500
Chemotherapy has no effect on these lesions in general; but 5-FU and mitomycin C have been recommended. Prognosis, in general, is better than for solid malignant tumors of the pancreas. Of 17 cases of cystadenocarcinoma of the pancreas presented by Warren and Hardy,9 38 percent lived five years or more and 23 percent lived ten years or more.
Conclusion Cystadenoma and cystadenocarcinoma are very rare cystic lesions of the pancreas. Their diagnosis is suspected on radiographic studies and confirmed at intervention and by pathological studies. Their treatment is based on the principle of total extirpation of the lesion and any involved areas. Palliative treatment can be achieved through internal drainage, marsupialization, radiotherapy, or chemotherapy. These lesions are interesting because of their relatively good prognosis. When adequately treated, a cure is definitely possible and survival of ten years or more is not exceptional. Literature Cited 1 Adloff M: Cystadenoma of the pancreas apropos of two recent cases, one treated by left pancreatectomy and the other by duodenocephalic pancreatectomy. Chirurgie 101 (51):303-310, 1863 2. Hartmann M: Kystes du pancreas. Rev de Chir 1 1:409, 1891 3. Sotti G: Adenocystoma papillifero del pancreas. (Arch. per le Sc. Mediche, 1906) Abstr. in: Central bl. f. alIg. Patti. u. Path. Anat.,
18:844 (Oct. 31), 1907 4. Lichtenstein L: Papillary cystadenocarcinoma of pancreas: Case report, with notes on classification of malignant cystic tumors of pancreas. Am J Cancer 21:542, 1934 5. Kennard HE: Papillary cystadenocarcinoma of the pancreas. Surgery 9:65-79, 1941 6. Mozan AA: Le cystadenoma du pancreas. Am J Surg 81:204, 1951 7. Cullen P, Remine WH, Dahlin DC: A clinicopathological study of cystadenocarcinoma of the pancreas. Surg Gynecol Obstet 122:117-189, 1963 8. Becker WF, Welsh R, Pratt HS: Cystadenoma and cystadenocarcinoma of the pancreas. Ann Surg 161:845-863, 1965 9. Warren KW, Hardy KJ: Cystadenocarcinoma of the pancreas. Surg Gynecol Obstet 127(4):734-736, 1968 10. Lewis A, Dormandy J: Cystadenoma du pancreas: Rapport de deux cases. Br J Surg 58:420, 1971 11. Vezzosi E: Cystadenocarcinoma of the pancreas. Minerva Chir 30(9):532-538, 1975 12. Catell R, Warren KW: Surgery of the Pancreas. Philadelphia, WB Saunders, 1953, p 1621 13. Ribet M, Wurtz A, Mortier F, et al: Cystadenomes et cystadecarcinomed du pancreas. Clin Chir Quest Chirugie 98(12): 736-743, 1972 14. Haukolh R, Melamed A: Cystadenoma of the pancreas: A report of two cases showing calcification. Radiology 63:234-245, 1950 15. Bravo L: A clinical pathological study of cystadenomas and cystadenocarcinoma of the pancreas, thesis. University of Minnesota Graduate School, 1947 16. Cornes JS, Azzopardi JG: Papillary cystadenocarcinoma of the pancreas with report of two cases. Br J Surg 47:139-144, 1959 17. Rowe PG: Papillary cystadenocarcinoma of the pancreas. Can Med Assoc J 74:724, 1956 18. Warren KW, Badosa F: Individualization in treatment of pancreatic cysts. Am Surg 39(10):555-561, 1973 19. Darmaillac P: Des kystes glandulaires du pancreas. These Bordeaux, No 46, 1939 20. Priesel A: Beitrage zur Pathologic der Bauchspreichel druse; mit besonderen Berucksichtigung adeno matoser Geschwulstbildungen: sowie der Antonomie der Langerhansschen Inseln. Z Pathol 26:453, 1922 21. Mercadier M: Methodes et indications du traitement des formations kystiques et psudokystiques du pancreas. J Chir 76:425, 1958 22. Glenner GC, Mallory GK: Cystadenoma and related non-functional tumors of pancreas: Pathogenesis, classification and significance. Cancer 9:980, 1956 23. Becker V: Carcinoma of the pancreas: Pathologie anatomy. Langenbecks Arch Chir 339: 219-227, 1975 24. Leborgne J, Le Need J, Mouseau P, et al: Considerations sur les cystadenomes multilocularies au niveau de la tete du pancreas: A propos d'une observation. Rev Fr Gastroenterol 83: 69-82, 1972 25. Piper CE, Remine WH, Prisestley JT: Adenomes kystiques du pancreas. JAMA 180: 648, 1962 26. Pinchuk LA: Tumores hipervascularizados del pancreas con diagnostico angiografico. Prensa Med Argent 60(40):1442-1447, 1971 27. Swanson GE: A case of cystadenoma of the pancreas studied by selective angiography. Radiology 81 (4):592-595, 1963 28. Pressman BD: Cystadenoma of the pancreas-a reappraisal of angiographic findings. Am J Roentgenol Radium Ther NucI Med 119(1): 115-120, 1963 29. Lardennois B, Flament JB, Hopner CL: Une observation de cystadenome de la queue du pancreas. Un signe angiographique des turmeurs de I'arriere cavite des epiploons: La rupture du cercle arteriel de la grande courbure. Bull Assoc Nord Lotharin Gienne Gastroenterol 3: 122, 1973 30. Debelut J, Payard JM: Cystadenome de la tete du pancreas. Chirurgie 96:506, 1970 31. Bieber WP, Albo RI: Cystadenoma of the pancreas: Use of arteriography in diagnosis. Radiology 80:776, 1963 32. Wolson HH: Ultrasonic characteristics of the cystadenoma of the pancreas. Radiology 119:203-205, 1976
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Cystadenomas and cystadenocarcinomas of the pancreas are rare, with few cases encountered by any one surgeon or institution. Cystadenomas account for less than ten percent of all cystic lesions of the pancreas with less than 300 examples reported in the literature. Cystadenocarcinomas represent one percent of all pancreatic cancers with very few cases reported. This report is a presentation of a 48-year-old black female who was treated at Meharry Medical College for cystadenocarcinoma of the pancreas, and is followed by a review of the world literature. Cystic lesions of the pancreas are generally rare. Proliferative cysts of the pancreas-cystadenoma and cystadenocarcinoma-are exceptionally rare. Very few cases have been reported in the literature. Because of the rarity of these lesions, the experience of any surgeon or institution is necessarily limited; thus these lesions always constitute an interesting and challenging problem. We report a case of cystadenocarcinoma of the pancreas, which was treated at the G. W. Hubbard Hospital of Meharry Medical College. This presentation is followed by a review of the world literature.
Case Report A 48-year-old black female was referred to the surgical service on February 23, 1977, because of an abdominal mass which she had first noted when lying prone about two weeks after Thanksgiving 1976. A few weeks later, she was able to feel the mass with her hand. The mass grew gradually to become a huge tumefaction filling the entire left aspect of the abdomen from the pelvis to the costal margin. She gave a history of occasional left flank pain which radiated to the anterior ab-
From the Department of Surgery, Meharry Medical College, Nashville, Tennessee. Requests for reprints should be addressed to Dr. Eddy S. Muzac, Department of Surgery, Meharry Medical College, 1005 18th Avenue North, Nashville, TN 37208.
domen. It was mild, lasted about one to two days, and dated back to September 1976. There was no history of nausea, vomiting, diarrhea, constipation, or bleeding from any orifice. There were no indications of trauma, pancreatitis, or drug addiction. There was a history of amenorrhea one month prior to admission and of a 20 lb weight loss in four months. She was para 3, gravida 3, and had had no abortions. Her menarche was at age 15 years; she experienced regular menses. There was no previous hospitalization or surgery, or history of diabetes mellitus, heart disease, or other systemic disease. Pertinent physical findings revealed moderate tachycardia with regular rhythm and an ejection murmur prominent at the apex with no gallop. The abdomen revealed a 25 x 20 cm tumefaction which extended from the pelvis to the costal margin and across the midline and filled the left anterolateral aspect of the abdomen. On palpation it was firm, irregular, nonmobile, and nontender. The superior surface was suggestive of a cystic lesion. There were no bruits or pulsation. On pelvic examination, movement of the cervix did not mobilize the tumor. The cervix was large and deviated to the left, but the uterus was not appreciably enlarged. Diagnostic studies revealed that blood morphology and chemistry values were normal except for a slight normocytic, normochromic anemia, SGOT of 81 m,u/ml, and a CEA of 1,125 ng/ml. A chest x-ray was normal except
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for elevation of the left hemidiaphragm. A flat plate x-ray examination of the abdomen revealed a large soft tissue mass in the left flank with a questionable calcification in the center. Intravenous pyelogram (IVP) showed deviation of the right ureter. Slight left side hydronephrosis was suggestive of compression of the left ureter by the abdominal mass. Barium enema showed marked depression of the splenic flexure and transverse colon. The upper gastrointestinal (UGI) series showed displacement and rotation of the stomach to the right with indention. Abdominal ultrasound showed a mass located in the upper compartments of the abdomen, which was not of ovarian or uterine origin. Spleen scan showed no involvement of that organ by the mass. The patient underwent exploratory surgery on March 3, 1977. A mass filling the entire left side of the abdomen was identified. It extended between the left side of the diaphragm superiorly, the pelvis inferiorly, and the right midclavicular line medially. The mass was cystic, partially covered by the gastrocolic omentum, and attached to the left hemidiaphragm, to the spleen which was in fact incorporated, and to the pancreatic tail (Figure 1). The stomach was displaced medially and the splenic flexure and transverse colon, inferiorly. The mass was anterior to the kidney. Both ovaries, the uterus (which was small), the liver, and the gallbladder were normal. The cyst was opened and five liters of light brown material were drained. Specimens were sent for culture and cytology. The interior lining of the cyst presented numerous papillary excrescences which were biopsied and sent for frozen section along with a mesenteric lymph node. The mass was resected, together with the spleen and the liver, and clips were placed in its bed before closing the abdomen in layers. The immediate postoperative course was uneventful. The pathologic diag495
Figure 1. Gross presentation of cystadenocarcinoma of the pancreas. Unilocular cyst with papillary excrescences in the cyst cavity
of the pancreas. Such a classification would present the pancreatic cysts in two principal groups: simple cysts and proliferative cysts. The latter would then essentially include cystadenoma and cystadenocarcinoma along with the very rare teratoma and vascular tumor. A classification based upon etiologic considerations, used by Vezzosi," includes five groups: (1) congenital cysts, (2) pseudocysts (traumatic or inflammatory), (3) retention cysts, (4) parasitic cysts, and (5) proliferative cysts (cystadenoma, cystadenocarcinoma). This classification is not different from that of Mahormer and Mattson as modified by Catell and Warren.'2 Personally, this author prefers the classification presented by Mallet-Guy and Mercadier in 1958 as cited by Ribet et al'3 (Table 1).
Incidence nosis was papillary cystadenocarcinoma of the pancreas (Figure 2). Following surgery, the patient received a course of chemotherapy (5FU). She was discharged in satisfactory condition. The CEA level was 520 in March and 136 in April. She was given 4,500 rads to the area outlined by clips. Subsequently, she received several courses of 5-FU until September 1977 when it was changed to mitomycin C. She was hospitalized in December 1977 for melena and upper gastrointestinal bleeding. Esophagogastroduodenoscopy showed bleeding from the stomach and duodenum. She died on January 10, 1978, of massive hemorrhage. An autopsy was not performed.
Discussion According to Adloff,' the first description of a pancreatic cystadenoma was given by Cruveilhier in 1863. In 1891, Hartmann,2 in France, described a cystadenoma of the pancreas with metastases to the liver. Sotti,3 in 1906 in Italy, presented a papillary cystadenoma with a spread to the peritoneum, the lungs, and regional 496
nodes. Lichtenstein4 in 1934 reported the first authentic case of cystadenocarcinoma of the pancreas recorded in America. Kennard5 presented the first review of the literature of cystadenocarcinoma of the pancreas in 1941, and found 25 documented cases. In 1951, Mozan' published an excellent review of the literature of cystadenoma of the pancreas and discussed 49 firmly documented cases, including one of his own. In 1963, Cullen et a17 reported the Mayo Clinic's experience with neoplastic cysts of the pancreas between 1908 and 1963. In 1965, Becker et all presented the experience of the Charity Hospital and of three other New Orleans hospitals for a 27-year period from 1938 through 1964. He found 164 recorded cases of cystadenoma and 65 cases of cystadenocarcinoma in the literature, since the first case reported by Frantz Lahey in 1927 (cited by Warren and Hardy).9 In 1971, in a presentation of the subject, Lewis and Dormandy'° could only record 251 cases of cystadenoma. The total cases reported in
the literature consist of approximately 300 cystadenomas and 130 cystadenocarcinomas. As part of a group of cystic formations, it becomes very useful to study the classification of cystic lesions
Haukolh and Melamed'4 emphasized that the true incidence of pancreatic cystadenoma and cystadenocarcinoma could not be known since many cases were undoubtedly buried in reports on pancreatic surgery, listed under erroneous diagnoses, or included in reports of unrelated nonneoplastic cysts. However, it is generally admitted that these lesions are rare. Cystadenomas account for approximately ten percent of all cystic lesions of the pancreas and are twice as frequent as cystadenocarcinomas. The latter are responsible for about one percent of all pancreas cancers. Bravo'5 could find records of only six cystadenocarcinomas in 202 cases of primary carcinoma of the pancreas at the Mayo Clinic. Cornes and Azzopardi'6 reported only two papillary cystadenocarcinomas in 8,500 necropsies at the Postgraduate Medical School of London in a 23-year-period. Rowe'7 reported one case of cystadenocarcinoma of the pancreas in more than 300,000 admissions to the Montreal General Hospital. Becker et a18 recorded seven cystadenomas and two cystadenocarcinomas in 2,184,427 admissions to Charity Hospital, New Orleans, during a 27-year-period. Warren and Hardy9 at the Lahey Clinic could find only 17 cystadenocarcinomas in 993 operations involving the pancreas during a 40-year-
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period. Warren and Badosa,18 at the same institution, reported only 12 cystadenomas and 15 cystadenocarcinomas in 256 patients with pancreatic cysts between 1927 and 1971. Darmaillac,19 Priesel,20 and Mercadier21 have also shown the rarity of these lesions. Our case of cystadenocarcinoma is the only one ever recorded at the G.W. Hubbard Hospital at Meharry Medical College in Nashville. All of the authors have emphasized the frank predominance of the proliferative cysts cystadenoma-cystadenocarcinoma-in women. Almost universally, these tumors occur in patients younger than those with solid carcinoma of the pancreas, which usually occurs in the fifth or sixth decade.
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Histogenesis The origin of the cystadenomas is uncertain. Although they constitute definite pathologic entities, very little is known of their pathogenesis. Trauma and inflammation apparently play no role in their formation. Glenner and Mallory,22 in a classic paper, state they have demonstrated that cystadenomas originate from the pancreatic ductal epithelium and describe the lesion as being true ductal cell adenomas of the cystic type. They classify nonfunctional pancreatic adenomas as duct adenomas, acinar adenomas, mixed adenomas, and fibroadenomas and include cystadenomas with solid duct cell adenomas. They state that the nonfunctional pancreatic adenomas originate deep in the parenchyma of the pancreas whereas cystic duct cell adenomas (cystadenomas) originate more peripherally.
Pathology The most common locations of the cyst, according to the majority of authors, are the tail and the body of the pancreas. As a matter of fact, of 81 cases of Becker,23 39 involved the tail of the glands, 14 the body, and 15 the head. There were ten cases of diffuse involvement of the pancreas. Cullen et a17 give the following distribution of 16 cases: body, four; head, three; tail, three; body and tail, two; and head and body, one. Theoretically, according to Becker et a18 these lesions may arise from heterotopic tissue; however, such
Figure 2. Microscopic appearance of papillary cystadenocarcinoma of the pancreas
cases were not described in the series. According to Kennard,5 the most common position into which the cyst grows is between the stomach and the transverse colon. Of 11 cases of Cullen et al,7 the presentation was behind the stomach in four; below the stomach through the gastrocolic omentum in two; in one case, above the stomach, through the gastrohepatic omentum below the transverse colon; and in one case, between the leaves of the transverse mesocolon, behind the transverse colon, and extending into the pelvis underneath the omentum to fill the entire left side of the abdomen. Mozan6 has described many types of cysts, ranging in size from very small to huge. The cases of Cullen7 vary from 8 to 24 cm in diameter. The character of the cyst content varies considerably. Often it is mucoid or serous and rarely clear. It has been described by different authors as thick colloid jelly,7 cloudy,9 straw colored, greenish, grayish, brown, or bloody,5 and chocolate or light brown in color. The volume of fluid varies in proportion to the size of the cyst, from 100 ml to gallons of fluid ("considerable fluid"'). In our case, the cyst cavity contained four to six liters of light brown material. One or more pancreatic enzymes may be found in the fluid, as reported by Kennard.5
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The gross appearance of pancreatic cystadenomas is fairly characteristic. Its surface is irregular, presenting a polycystic aspect. Very often, the tumor is surrounded by widely dilated veins due to local pressure, presumably from compression of the splenic vein. These vessels may constitute a serious obstacle to the surgeon at the time of operation. This vascularity was a feature of our case. Depending upon the size and location of the tumor, there may or may not be considerable distortion and/or displacement of the surrounding viscera. The cut surface is almost classical and demonstrates the different morphological varieties of cyst. Indeed one can find the uniloculated (serous of Mercadier), the pauciloculated (few cavities), and the multiloculated (numerous cavities) cysts or mucoid cysts. The uniloculated cyst is typical for Mercadier.21 The multiloculated is the classical form described in most pathology treatises. This is the centroacinar cystadenoma of Becker et al.8 The tumor is occasionally less markedly cystic, grossly presenting a softer, more cellular yellowish-gray cut surface. This is the papillary cystadenoma in which the cyst is filled with irregular papillary masses or excrescences. The papillary excrescences have been 497
Table 1. Classification of Pancreatic Cysts13
I. Pseudocysts 1. Traumatic 2. Apoplectic 11. Retention Cysts 1. Obstruction by stone 2. Obstruction by neoplasm 3. Obstruction by scar Ill. True Cyst 1. Embryonic cysts A. Ectodermal or dermoid B. Endodermal or enteroid C. Ecto and endodermal cystic teratoma 2. Neoplastic cysts (from acinar or ductal epithelium) A. Cystadenoma B. Cystadenocarcinoma 3. Parasitic cysts or hydatid cysts 4. Mesenchymatous cysts A. Hemangioma B. Lymphangioma C. Hemangioendothelioma
viewed by some authors as a sign of malignancy or potential malignancy. The overall appearance of cystadenoma and cystadenocarcinoma is identical. Only microscopic analysis may make the difference. However, one may suspect malignancy if the following signs are present: papillary excrescences in cyst cavity, invasion of surrounding organs, local lymph node involvement, and distant metastases. According to Warren and Hardy,9 common sites of metastases, when they occur, include the liver, peritoneum, lesser omentum, transverse mesocolon, spleen, and left kidney.
Microscopic Study The fibrous capsule of the cyst is generated by compression and progressive atrophy of the pancreatic lobules in contact with the tumor. It may still contain a few ducts and islands of Langerhans like any sclerotic process of the pancreas. The radiating trabeculae between the cyst have the same collagen consistency as the surrounding capsule to which they are connected. The oldest ones have become hyalosclerotic, poor in blood ves498
sels, and epithelial. Some others are more congestive and thick with more cellularity and epithelial destruction due to a mutilating inflammatory reaction. They may show signs of stromal calcification of varying importance probably due to the organization of small hemorrhages and inflammatory reactions. The lining of the cyst is variable from one case to another and may vary from one small unit to another one. In the most typical case, the lining cells are low cuboidal. True papillary formation does not appear here. These epithelial cells have been linked to the flat cells of the terminal ductules of the pancreas or to centroacinar cells. In some tumors the epithelium is so flattened as to resemble vascular epithelium. This, together with the scattering of lymphocytes in the stroma and some degree of hemorrhagic effusion in the cystic cavity, may mislead to the false diagnosis of cystic lymphangioma, angioendothelial sarcoma, or vascular tumor. However, generally repeated sections may reveal definite cuboidal epithelium and the true nature of the tumor. Finally, in certain cysts presenting intracystic papillary excrescences, the lining cells are columnar, resembling large pancreatic duct epithelium. The lining may also resemble intestinal epithelium or simulate the epithelium of
the pseudomucinous cystadenoma of the ovary. This type is papillary cystadenoma or proliferative cystadenoma. Certain authors feel that this is a premalignant form and believe that cystadenomas lined by tall columnar epithelium or intestinal-like epithelium are the ones which undergo malignant change and generate the cystadenocarcinomas. In cystadenocarcinomas, papillary growths of the lining epithelium are frequently seen but, while indicative of proliferative activity, are not by themselves sufficient for a diagnosis of malignancy in a cystadenoma of dubious appearance. 16 The criteria of malignancy have been well described by Cullen7 and Comes and Azzopardi. '6 These authors state that in the absence of metastases, perineural invasion, extracapsular extension, areas of frank anaplasia, or other unequivocal evidence of malignancy, evidence of malignant changes must be sought in the presence of focal areas showing pseudostratification or true stratification, nuclear hyperchromasia and irregularity, increase in nuclear size, mitotic activity, cellular differentiation, and presence of anaplastic areas with bizarre tumor cells and neoplastic giant cells.
Clinical Features The clinical features of pancreatic cystadenoma and cystadenocarcinoma are essentially those of a pancreatic cyst in general and are the result of pressure on contiguous structures by the slowly enlarging pancreatic tumor (Table 2). The evolution before diagnosis is generally progressive and insidious. Often the tumor will manifest itself after a long period of evolution. Becker et a18 state that over one third of patients had symptoms for more than 24 months before the diagnosis was established. The average duration of symptoms is, in general, approximately 18 months. The presence of an abdominal mass constitutes the most important clinical manifestation of the disease. It is reported in 80 to 90 percent of all cases. Often it is noticed by the patient himself; one study reported a 50 percent incidence of self discovery.8 The mass is found in the left upper quadrant or
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epigastrium in most instances. In the case of a tumor of the head of the pancreas, it may be felt in the right upper quadrant. Classically, the mass is irregular, firm, nontender, grossly round, and eventually nodular. This tumor is also mobile in more than 50 percent of cases, a feature which is so important that it becomes possible to mobilize the mass vertically and transversally. In certain instances, the mass may be palpated in the left lumbar area and mistaken for a renal mass, which may lead to a left lobotomy. Pain, the chief complaint in 50 percent of cases reported by Becker et al,8 is generally variable in location in the epigastrium or in the left upper quadrant. It may radiate to the back. Dyspepsia is recorded in 75 percent of cases and is generally manifested by flatulence (postcibal), nausea, and occasional vomiting. Diarrhea is reported in 15 percent of the cases and may lead one to think of a pancreatic involvement. The percentages given for weight loss by authorities differ widely; it was found in 25 percent of cases reported by Leborgne et al,24 and in 3 of 20 cases by Piper et al.25 In our patient, the weight loss was 25 lb in four months. Jaundice was present in 3 of 28 cases reported by Becker et al.8 It is generally explained on the basis of compression of the biliary system by a mass located in the head of the pancreas. Associated disorders, which include a case each of duodenal ulcer, pancreatitis, and jejunal diverticular, have been reported by Cullen et a17 in a review of 17 cases of cystadenocarcinoma. Some articles have additionally stressed the association of symptoms such as sterility, obesity, thyroid dysfunction, and diabetes mellitus with pancreatic cystadenomas. The complications of these tumors are related to their location and size and to the involvement of the surrounding organs from compression or infiltration by the neoplastic process. Compression of surrounding organs, ie, duodenal obstruction resulting from a
cystadenoma or cystadenocarcinoma located in the head of the pancreas, may occur. Common duct obstruction may occur through compression of its retropancreatic portion. This is seen more often in cystadenocarcinoma of the head of the pancreas. Hemorrhage may be one of the most severe complications of the lesions in the course of
their evolution. Different mechanisms may produce hemorrhage, such as segmental portal hypertension from compression or involvement of the splenic vein. Portal hypertension (segmental) is seen more frequently in tumors of the body of the pancreas.24 Infiltration of the gastric and the duodenal mucosa by cystadenocarcinoma with subsequent hemorrhage is frequently found.25 Cystadenoma in ectopic pancreatic tissue in the duodenum is listed by Leborgne et a124 as a possible cause of intestinal bleeding. Finally, intracystic hemorrhage remains a potential cause of bleeding in both cystadenoma and cystadenocarcinoma.24 Complications in the cysts themselves include intraperitoneal rupture and infection with abscess formation.
Diagnostic Procedures The laboratory is generally silent. In particular, the serum and urinary amylase are absolutely negative. However, instances of diabetic or paradiabetic states may be found. Besides, the hematology may be consistent with a certain degree of hypersplenism, particularly in the case of segmental portal hypertension with splenomegaly. The various radiographic studies may show the tumor in certain instances as a round homogenous mass modifying the gaseous patterns of the digestive tract. Exceptional cases may show striking calcification of the tumor. In a case reported by Haukolh and Melamed, 14 calcific deposits located in the head of the pancreas were arranged in a radiating "sunburst" pattern about a central, completely calcified nidus. Sometimes the calcifications appeared as small irregular particles scattered haphazardly throughout the tumor. Leborgne et a124 stated that calcifications are best diagnosed on lateral views and are present in only ten percent of cases. The UGI series may show displacement upward and forward of the stomach. Sometimes, in the case of a tumor of the head of the pancreas, the UGI series may show displacement of the antrum, duodenal stenosis, and/or widening of the C loop of the duodenum. Whipple (cited by Catell and Warren12) suggested giving barium simulta-
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Table 2. Signs and Symptoms % of Cases Abdominal mass Dyspepsia, nausea, vomiting Pain Weight loss Diarrhea Jaundice Diabetes
85 75 50 25 15 12 9
neously by mouth and rectum. X-ray will show the cyst bulging between the stomach and the transverse colon. The barium enema generally shows inferior displacement of the transverse colon and the splenic flexure. The cholangiography will demonstrate a compression of the common duct and the biliary system. The intravenous pyelogram shows signs of compression of the left ureter, which is sometimes accompanied by hydronephrosis (in the tail and body of the pancreas). Angiographic studies reveal important information concerning the nature and location of these tumors. Celiac and mesenteric selective arteriography have been described by Pinchuck,26 Swanson,27 Pressman,28 Lardennois et al,29 Ribet et al,13 and Debelut.30 Translumbar aortography has been used by Bieber and Albo.3' Lardennois29 has described a rupture of the arterial circle of the greater curvature of the stomach. The right gastroepiploic artery is pushed upward and to the right with the colon, resembling the letter S, the middle portion of the S being constituted by the hepatic artery and the splenic artery. This configuration is consistent with a retroperitoneal location of the tumor. The venous phase will show an extensive capillary blush in the tumor and occasional displacement of the portal vein. Certain signs, like hypervascularization of the tumor and the presence of hemorrhagic plaques inside the cyst, will indicate a malignant lesion. But these signs have been described in both cystadenoma and cystadenocarcinoma. In the case of a tumor of the distal pancreas, splenoportography is the best angio499
graphic exploration. Celiac and mesenteric selective arteriography may reveal the presence of a retro or intrapancreatic right hepatic artery which is found in 20 percent of cases.24 Its localization may be important if a duodenopancreatectomy is considered. Endoscopic retrograde cannulation of the pancreatic duct may greatly aid in the diagnosis of these tumors in the future. Splenic and pancreatic scan may show noninvolvement of the spleen and the relationship of the tumor with the pancreas. Ultrasonic characteristics of cystadenoma of the pancreas have also been explored: a sonolucent lesion with strong through transmission, silent irregularity of the wall, and an internal septum should suggest cystadenoma.2
vital structure like the portal vein or the splenomesenteric junction in the case of a very old patient or a patient with poor general condition. Warren and Hardy9 favor cystogastrostomy or cystojejunostomy. Mercadier21 states that a cystoduodenostomy is more physiologically functional. Survivals of several years have been reported after internal drainage for cystadenocarcinoma, which attests to the slow growing character of this tumor. Biopsy, frozen section, puncture, or opening of the cyst are not recommended because of the risk of spillage and seeding.
Radiotherapy As a palliative treatment, radiotherapy may be helpful in the case of extensive lesions or as an adjuvant therapy in addition to operation.9
Chemotherapy Treatment Treatment varies with the location of the lesion and the age and general condition of the patient. Surgical treatment is rather classical and includes several possibilities.
Definitive Surgical Treatment Enucleation of a cystadenoma may be possible if there is a definite capsule which will allow complete and easy removal en bloc. Excision with a margin of pancreatic tissue is advocated for both cystadenoma and cystadenocarcinoma. This procedure is very easy in the case of a pedunculated cyst with a small base. Distal pancreatectomy with splenectomy is advocated for tumors of the tail and body of the pancreas. Duodenopancreatectomy is the preferred treatment for lesions of the head of the pancreas. This is the price to pay to cover in the case of the benign variant (cystadenoma) because of serious potential degeneration. Total duodenopancreatectomy may be considered for diffuse lesions.
Palliative Surgical Treatment Marsupialization is not employed when one is operating for cure even in the case of cystadenoma. Risk of malignant degeneration is the reason for contraindication. Internal drainage considered as a palliative procedure would endanger a 500
Chemotherapy has no effect on these lesions in general; but 5-FU and mitomycin C have been recommended. Prognosis, in general, is better than for solid malignant tumors of the pancreas. Of 17 cases of cystadenocarcinoma of the pancreas presented by Warren and Hardy,9 38 percent lived five years or more and 23 percent lived ten years or more.
Conclusion Cystadenoma and cystadenocarcinoma are very rare cystic lesions of the pancreas. Their diagnosis is suspected on radiographic studies and confirmed at intervention and by pathological studies. Their treatment is based on the principle of total extirpation of the lesion and any involved areas. Palliative treatment can be achieved through internal drainage, marsupialization, radiotherapy, or chemotherapy. These lesions are interesting because of their relatively good prognosis. When adequately treated, a cure is definitely possible and survival of ten years or more is not exceptional. Literature Cited 1 Adloff M: Cystadenoma of the pancreas apropos of two recent cases, one treated by left pancreatectomy and the other by duodenocephalic pancreatectomy. Chirurgie 101 (51):303-310, 1863 2. Hartmann M: Kystes du pancreas. Rev de Chir 1 1:409, 1891 3. Sotti G: Adenocystoma papillifero del pancreas. (Arch. per le Sc. Mediche, 1906) Abstr. in: Central bl. f. alIg. Patti. u. Path. Anat.,
18:844 (Oct. 31), 1907 4. Lichtenstein L: Papillary cystadenocarcinoma of pancreas: Case report, with notes on classification of malignant cystic tumors of pancreas. Am J Cancer 21:542, 1934 5. Kennard HE: Papillary cystadenocarcinoma of the pancreas. Surgery 9:65-79, 1941 6. Mozan AA: Le cystadenoma du pancreas. Am J Surg 81:204, 1951 7. Cullen P, Remine WH, Dahlin DC: A clinicopathological study of cystadenocarcinoma of the pancreas. Surg Gynecol Obstet 122:117-189, 1963 8. Becker WF, Welsh R, Pratt HS: Cystadenoma and cystadenocarcinoma of the pancreas. Ann Surg 161:845-863, 1965 9. Warren KW, Hardy KJ: Cystadenocarcinoma of the pancreas. Surg Gynecol Obstet 127(4):734-736, 1968 10. Lewis A, Dormandy J: Cystadenoma du pancreas: Rapport de deux cases. Br J Surg 58:420, 1971 11. Vezzosi E: Cystadenocarcinoma of the pancreas. Minerva Chir 30(9):532-538, 1975 12. Catell R, Warren KW: Surgery of the Pancreas. Philadelphia, WB Saunders, 1953, p 1621 13. Ribet M, Wurtz A, Mortier F, et al: Cystadenomes et cystadecarcinomed du pancreas. Clin Chir Quest Chirugie 98(12): 736-743, 1972 14. Haukolh R, Melamed A: Cystadenoma of the pancreas: A report of two cases showing calcification. Radiology 63:234-245, 1950 15. Bravo L: A clinical pathological study of cystadenomas and cystadenocarcinoma of the pancreas, thesis. University of Minnesota Graduate School, 1947 16. Cornes JS, Azzopardi JG: Papillary cystadenocarcinoma of the pancreas with report of two cases. Br J Surg 47:139-144, 1959 17. Rowe PG: Papillary cystadenocarcinoma of the pancreas. Can Med Assoc J 74:724, 1956 18. Warren KW, Badosa F: Individualization in treatment of pancreatic cysts. Am Surg 39(10):555-561, 1973 19. Darmaillac P: Des kystes glandulaires du pancreas. These Bordeaux, No 46, 1939 20. Priesel A: Beitrage zur Pathologic der Bauchspreichel druse; mit besonderen Berucksichtigung adeno matoser Geschwulstbildungen: sowie der Antonomie der Langerhansschen Inseln. Z Pathol 26:453, 1922 21. Mercadier M: Methodes et indications du traitement des formations kystiques et psudokystiques du pancreas. J Chir 76:425, 1958 22. Glenner GC, Mallory GK: Cystadenoma and related non-functional tumors of pancreas: Pathogenesis, classification and significance. Cancer 9:980, 1956 23. Becker V: Carcinoma of the pancreas: Pathologie anatomy. Langenbecks Arch Chir 339: 219-227, 1975 24. Leborgne J, Le Need J, Mouseau P, et al: Considerations sur les cystadenomes multilocularies au niveau de la tete du pancreas: A propos d'une observation. Rev Fr Gastroenterol 83: 69-82, 1972 25. Piper CE, Remine WH, Prisestley JT: Adenomes kystiques du pancreas. JAMA 180: 648, 1962 26. Pinchuk LA: Tumores hipervascularizados del pancreas con diagnostico angiografico. Prensa Med Argent 60(40):1442-1447, 1971 27. Swanson GE: A case of cystadenoma of the pancreas studied by selective angiography. Radiology 81 (4):592-595, 1963 28. Pressman BD: Cystadenoma of the pancreas-a reappraisal of angiographic findings. Am J Roentgenol Radium Ther NucI Med 119(1): 115-120, 1963 29. Lardennois B, Flament JB, Hopner CL: Une observation de cystadenome de la queue du pancreas. Un signe angiographique des turmeurs de I'arriere cavite des epiploons: La rupture du cercle arteriel de la grande courbure. Bull Assoc Nord Lotharin Gienne Gastroenterol 3: 122, 1973 30. Debelut J, Payard JM: Cystadenome de la tete du pancreas. Chirurgie 96:506, 1970 31. Bieber WP, Albo RI: Cystadenoma of the pancreas: Use of arteriography in diagnosis. Radiology 80:776, 1963 32. Wolson HH: Ultrasonic characteristics of the cystadenoma of the pancreas. Radiology 119:203-205, 1976
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